Nuclear factor I-C aggravates acute myelogenous leukemia by inhibiting SRY-box transcription factor 1 to activate autophagy

Cong Luo, Zeyu Luo, Junjun Li, Feng Wen, Yixiong Cao, Qiong Liu,  Xingxing Long

Abstract:

Despite advances in chemoradiotherapy and hematopoietic stem cell transplantation, the treatment of acute myeloid leukemia (AML) remains challenging due to significant side effects and poor prognosis. This study aimed to investigate the role of nuclear factor I-C (NFIC) in AML progression by evaluating whether NFIC exacerbates AML through the inhibition of SRY-box transcription factor 1 (SOX1) and activation of autophagy, thereby providing potential insights for clinical treatment. NFIC and SOX1 expression levels in AML and normal samples were analyzed using bioinformatics, ELISA, RT-qPCR, and western blotting, and the interaction between NFIC and SOX1 was assessed through RNA pull-down and RNA-binding protein immunoprecipitation assays. Moreover, CCK-8 assay, FITC/PI apoptosis detection, immunofluorescence staining, RT-qPCR, and western blotting were conducted to assess cell viability, apoptosis, and the expression of NFIC, SOX1, Bax, Bcl-2, LC3-I, LC3-II, p62, and Beclin-1 following gene transfection. NFIC expression was significantly upregulated in AML samples while SOX1 expression was downregulated compared to normal controls. High NFIC levels were associated with poor prognosis in AML patients, and it was found to regulate SOX1 expression in KG-1 and NB4 cells negatively. Silencing NFIC or overexpressing SOX1 resulted in reduced cell viability and autophagy, and increased apoptosis in KG-1 and NB4 cells. Importantly, NFIC knockdown did not affect apoptosis in bone marrow mononuclear cells. The adverse effects of NFIC overexpression were reversed by SOX1 overexpression, highlighting the interplay between these factors in AML. This study demonstrates that NFIC promotes AML progression by activating autophagy and suppressing apoptosis in KG-1 and NB4 cells by inhibiting SOX1, providing a potential basis for therapeutic strategies targeting NFIC and SOX1 in AML.